970 FEKETE A. KE1u.yI: POSTMORTEM BLOOD SUGAR .4i..D Uiu. Nimoc. . 92 Postmortem Blood Sugar and Blood Urea Nitrogen Determinations JOHN F. FEKETE, M.D.* and NORBERT A. KERENYI, M.D.,t Frederiatcm, N.B.

ABSTRACT SOMMAIRE Glucose and urea nitrogen determinations On a proc.d6 dans 160 cas . l'analyse post were made on blood and cerebrospinal fluid mortem du sucre et de l'azote ur6ique dans samples collected during 160 postmortem le sang et le liquide c6phalo-rachidien examinations in order to determine the use- (LCR) afin d'6tablir l'utilit6 de ces 6preuves fulness of such tests in diagnosing diabetes en vue du diagnostic de diab.te et d'ur6mie and uremia at the time of autopsy. The re- au moment de Ia n6cropsie. Il ressort de sults indicated that: (1) Blood is unsuitable cette .Stude que 1) le sang ne convient pas for postmortem glucose determination, and pour 6tablir la glyc6mie, aucune valeur no postmortem normal can be established. normale de glyc6mie post-mortem ne pou- (2) Cerebrospinal fluid gave more uniform vant .tre fixSe; 2) le LCR a donn6 des but very low glucose values. (3) Diabetics valeurs de glucose plus uniformes, mais as a group had very high postmortem glu- tr.s faibles; 3) les diab6tiques en tant que cose levels but showed a marked overlap groupe pathologique accusaient de tr.s with non-diabetics. (4) Infants less than 3 fortes glyc6mies, mais ces valeurs chevau- months of age showed high postmortem chaient largement sur le groupe des non glucose values. (5) Postmortem blood urea diab6tiques; 4) les proportions post-mortem nitrogen and cerebrospinal fluid urea nitro- de glucose 6taient tr.s 6lev6es chez les gen levels were within normal limits in previously nourrissons de moins de 3 mois; 5) les healthy persons who died sud- valeurs de l'azote ur6ique, dans le sang et denly from accidental causes. (6) Hospital le LCR, 6taient dans la gamme normale de autopsy cases had high urea nitrogen levels. personnes bien portantes (7) Postmortem urea nitrogen levels higher qui .taient mortes than 100 mg.% were indicative subitement dans des accidents. Les valeurs of uremia. post-mortem d'azote ur6ique, 6taient 6lev6es dans les autopsies effectu6es sur des per- sonnes mortes .i l'h6pital; 7) une valeur post-mortem d'azote ur6ique sup6rieure . 100 mg.% portait . croire . Ia presence d'ur6mie. Canad. Med. Ass. J. May 1, 1965, vol. 92 Fii.urni. AND KIIaUiNYI: POSTMORTEM BLOOD SUGAR AND UREA NImoGi..i 971 in the refrigerator until the chemical determinations existed. Readings over 150-200 mg. % signify pre- were carried out. mortem hyperglycemia. The presence of menin- The blood and cerebrospinal fluid sugar was de- gitis and encephalitis during life renders the termined by Technicon Autoanalyzer, employing a cerebrospinal fluid unsuitable for postmortem modification of W. S. Hoffman's potassium fern- glucose determination. cyanide-potassium ferrocyanide oxidation reduction Diabetics have, as a group, much higher post- reaction.5 Blood urea nitrogen determinations were mortem blood and cerebrospinal fluid sugar levels also performed on the Technicon Autoanalyzer by than normal persons. In individual cases, there is, the carbomido-diacetyl method of Skeggs et al.5 however, a marked overlap with the normals. Pre- Other tests were performed on selected samples. mortem hypoglycemia cannot be recognized either by postmortem blood sugar or by postmortem RESULTS AND CoNcI.usloNs cerebrospinal fluid sugar determinations (Table Postmortem Blood Sugar III). Of the total of 160 cases, 102 were considered to TABLE III.-POsmIoRTEM GLUCOSE IN MG.% have normal carb6hydrate metabolism (normal Average of Range of Average Range of premortem blood sugar values, negative urine mean values mean values spread spread Normaigroup. 96.8 7.5-567 86.4 0-594 sugar, negative clinical history); nine were dia- Accidental death. 105.5 15.0-260 ** Cases not kept in betics; 29 were infants under 3 months of age. refrigerator.108.1 24.3 - 260 156.4 3 -422 Fifteen Diabetics.212.6 10.0-567 104.6 0-250 cases were brought in from outside the Infants under 3 months hospital and were not kept in the refrigerator until ofage.170.9 14.5-472 127.3 1-273 the time of the autopsy. Eighteen persons died sudden accidental deaths; five cases were found un- Newborns and infants under the age of 3 months satisfactory and were not used (Table I). have a significantly higher postmortem blood glu- cose than normal adults, which is all the more TABLE 1.-POSTMORTEM GLUCOSE interesting because, in vivo, newborns and very Total number of cases. 160 young infants have a blood sugar lower than the Normal group. 102 normal adult level. This fact has never been re- (accidental death). 18 Diabetics. 9 ported before and we cannot offer a good explana- Infants under 3 months of age. 29 tion for this phenomenon. Bodies not kept in refrigerator. 15 Unsuitable. We found that, in the first 36 hours after death, 5 there is no correlation between the level of post- mortem blood sugar and the time elapsed since The mean blood sugar of the normal group was death or the temperature at which the body was 96.8 mg. %; within this group, those who had kept. There is, however, a greater spread of values accidental deaths had a mean of 105.5 mg. %. in cases where the bodies were not kept in the The mathematical average of samples taken from refrigerator. the jugular veins, iliac veins and the left side of the heart probably represents the theoretical "true" Infusion of a 5% solution of glucose in the last postmortem blood sugar. The individual values, 12 hours before death did not raise the postmortem however, varied widely. Samples from the right side blood sugar significantly. In a few such cases, how- of the heart yielded much higher readings with ever, glucose was found in postmortem urine much greater spread (Table II). samples. The postmortem blood sugar level is governed by several factors, some of which raise it and some TABLE 11.-POSTMORTEM GLUCOSE (NORMAL GROUP) of which lower it. Table IV shows some of these IN MG.% factors and the way in which they influence post- Lowest Highest value value Mean mortem blood sugar levels."4 Postmortem glyco- lysis may occur rapidly and extremely low values Jugular veins. 6 358 80.3 may be obtained within a few hours after death. Iliac veins. 5 362 65.7 Left heart. 0 489 81.4 On the other hand, the concentration of sugar in Right heart. 4 735 148.0 the right heart blood may increase post mortem, Cerebrospinal fluid. 8 117 42.5 probably owing to hepatic glycogenolysis.2 Invasion of dead tissues by intestinal bacteria occurs in three The postmortem level of the cerebrospinal fluid to four hours at room temperature and is followed (CSF) glucose is lower than the blood glucose by bacterial glycogenolysis, which elevates the (42.5 mg. % average), with a smaller spread of blood sugar considerably. The above-mentioned values. In the first 36 hours after death, in our considerations clearly indicate that, contrary to experience, the CSF glucose never participates in Harrison's3 statement, blood is unsuitable for post- the postmortem rise of blood sugar. It has a mortem glucose determinations and the cerebro- tendency, however, to fall very rapidly, shortly spinal fluid has only a very limited value in this after death, even when premortem hyperglycemia respect. Canad. Med. Ass. J. 972 FEIo&m AND KERENYI: POSTMORTEM BLOOD SUGAR AND UREA NITROGEN May 1, 1965, vol. 92

TABLE IV.-FACTORS INFLUENCING POSTMORTEM BLOOD kidney and liver in the dying results, in most cases, SUGAR in a varying degree of extrarenal azotemia. A. Factors tending to raise postmortem blood sugar Infants between the ages of 0 and 3 months 1. Liver glycogenolysis showed a lower postmortem blood urea nitrogen 2. Bacterial breakdown of carbohydrates in the gastro- intestinal tract and in the tissues than the ad.lts in the series. In the group with kidney disease and uremia, the B. Factors tending to lower postmortem blood sugar markedly 1. Oxidative glycolysis by cells still living postmortem blood urea nitrogen was 2. Anaerobic glycolysis by dying cells and free enzymes elevated, and in most instances it was significantly 3. Anaerobic glycolysis by bacteria higher than the last premortem blood urea nitrogen C. Factors influencing A and B value. 1. Time elapsed since clinical death In the last group of cases (those with liver 2. Temperature of the body postmortem 3. Amount of liver glycogen available (liver disease, failure) we found that the average nutritional state, etc.) blood urea nitrogen was almost as high as in cases 4. Number of bacteria present at the time of death with renal failure; no case in this group had a (septicemia, gas gangrene, etc.) 5. Amount of food present in the gastrointestinal tract lower reading than 100 mg. %. The only common at the time of death, etc. denominator in these subjects was a significant degree of hepatic failure. The highest postmortem blood urea nitrogen readings were obtained in two Postmortem Blood Urea Nitrogen cases of infectious hepatitis with hepatic coma Of the 160 patients, 74 died of chronic or acute (257 mg. % and 243 mg. %, respectively). No diseases, and 18 previously healthy persons had macroscopic or microscopic evidence of kidney sudden, accidental deaths. Nineteen had kidney disease was found, but one had a high blood urea disease with elevated blood urea nitrogen; 12 Md nitrogen two days before death. hepatic disease with liver failure; two had extra- There is no ready explanation for these high post- renal azotemia. There were 27 infants between the mortem blood urea nitrogen readings. It is well ages of 0 and 3 months. Eight cases were unsatis- known that the liver is the sole site of urea fonna- factory and were not used (Table V). tion, and in acute yellow atrophy and other types of severe liver damage in which extensive loss of functional liver tissue occurs, decreased blood urea TABLE V.-POSTMORTEM UREA NITROGEN nitrogen values are noted.8 The carbamido-diacetyl method of blood urea nitrogen determinations, used in our series, measures urea directly and ammonia does not take part in the reaction.5 For this reason, an increase of blood ammonia could not explain these high blood urea nitrogen levels. It seems that unknown extrarenal factors play a part in the rise of postmortem blood urea nitrogen and that secondary impairment of the excretory function of the kidney follows liver failure. Those who support the concept of a hepatorenal syndrome would probably accept this explanation. In conclusion, the postmortem blood urea nitro- gen values were found to be in close correlation with premortem values and were constant irrespec- tive of the site of collection and, within the first 24-36 hours, regardless of the time elapsed after death. The cerebrospinal fluid also yielded very constant urea nitrogen values. In cases of sudden death in the absence of disease, the upper limit of postmortem normal is 25-30 mg. %.

SUMMARY The interpretation of postmortem blood chemistry values is often difficult. This problem has not been investigated recently and only occasional references are found in the medical literature.2' .. . In the present study, specimens were collected during 160 postmortem examinations. Specimens in- cluded blood taken from the right side of the heart, the left side of the heart, the external jugular veins, the iliac veins, and cerebrospinal fluid. Blood sugar and Canad. Med. Ass. .* FEKETE AND K.a..yi: POSTMORTEM BiQoD SUGAR AND UREA Nimoc... 973 May 1, 1965, voL 92 blood urea nitrogen determinations were carried out a marked overlap with normals and, therefore, high simultaneously on every sample. Other tests were per- postmortem blood sugar values cannot be used to formed on selected cases. establish antemortem hyperglycemia. A few of our findings were at variance with previous Perhaps our most interesting finding is that new- reports. borns and infants below 3 months of age show a Postmortem blood urea nitrogen results were uniform significantly higher postmortem blood glucose level regardless of the sites of collection. They were well than normal adults, 170.9 mg. % compared with 96.8 within normal limits in previously healthy persons who mg. %. died sudden accidental deaths. Postmortem blood urea nitrogen values higher than 100 mg. % always in- REFERENCES 1. FEARON, W. R.: An introduction to biochemistry, 3rd ed., dicated renal or extrarenal uremia. It is of considerable William Heinemann Ltd., London, 1949, P. 329. interest that persons who died of liver failure also had 2. HAMILTON-PATERSON, J. L. AND JOHNSON, E. W. M.: J. Path. Bact., 50: 473, 1940. high postmortem blood urea nitrogen. 3. HARRISON, G. A.: Chemical methods in clinical medicine, Our results indicate that blood is unsuitable for 4th ed., J. & A. Churchill, Ltd., London, 1957, p. 184. 4. HARROW, B. AND MAZTJR, A.: Textbook of biochemistry, postmortem glucose determination, and no postmortem 7th ed., W. B. Saunders Company, Philadelphia, 1958. 5. Technicon Instrument Company: Instruction manual for normal of this substance can be established. Samples technicon autoanalyser. Method File N-la and N-2a, taken from the cerebrospinal fluid gave more uniform Chauncey, New York, 1963. 6. LEVINSON, S. A. AND MACFATE, R. P.: Clinical laboratory and lower sugar values than blood samples. diagnosis, 6th ed., Lea & Febiger, Philadelphia, 1961, p. 44 and 47. Diabetics as a group show much higher blood sugar 7. NAUMANN, H. N.: Amer. J. Olin. Path., 20: 314, 1950. values (212.6 mg. % mean value). There is, however, 8. Idem: Arch. Path. (Chicago), 47: 70, 1949.

CANADIAN JOURNAL OF SURGERY The April 1965 issue of the Canadian Journal of Surgery contains the following original articles, case reports and experimental surgery: History of Canadian Surgery: Irving Heward Cameron (1855-1933): Professor of Surgery, University of Toronto, 1897-1920-C. W. Harris. Original Articles: Percutaneous transhepatic cholangiography-M. Parent, M. Dufresne and G. Dutron. Tibial plateau fractures-T. W. Barrington and F. P. Dewar. Gastric cooling and hepatic function-N. B. Hersh- field, J. F. Lind and H. A. Hildes. Malignant pericardial effusion: review of hospital experience and report of a case successfully treated by talc poudrage-B. S. Goldman and F. G. Pearson. The obstructive factor in urethral diverticulum in paraplegics-J. G. Connolly and A. W. Bruce. Thermal burn encephalopathy-W. K. Lindsay, E. G. Murphy and D. C. Birdsell. Review Article: Surgery of intracranial berry aneurysms: a review-K. K. Jam. Case Reports: Stomach duplication-J. P. Fleming and J. N. Ward-McQuaid. Acute alcoholic poisoning: a complication of gastric hypothermia-B. J. F. Perey, S. J. Helle and L. D. MacLean. Rupture of the interventri- cular septum due to blunt trauma-M. Tascon-Alonso and 0. Rostrup. Experimental Surgery: Experimental studies on fibrosis of the sphincter of Oddi and on sphincterotomy- P. Prudhomme, P. Nioff, S. C. Skoryna and D. R. Webster. Studies on lambs of the development of an artificial placenta: review of nine long-term survivors of extracorporeal circulation maintained in a fluid medium-J. C. Callaghan, E. A. Maynes and H. R. Hug. Fat embolism: its production and source of fat-K. S. Morton and M. J. Kendall. Experimental reconstruction of the cervical esophagus with a free enteric graft-W. G. Beattie, F. N. Brown, J. E. Devitt and I. J. Vogelfanger. The Canadian Journal of Surgery is published quarterly by The Canadian Medical Association. Subscription rates are $10.00 a year ($5.00 a year for recognized postgraduate trainees in surgery) or $2.50 for individual copies. Yearly subscriptions and back issues are available on request from the Canadian Journal of Surgery, C.M.A. House, 150 St. George Street, Toronto 5, Ont.